Advances in Palladium-Catalyzed Carboxylation Reactions

In this short review, we highlight the advancements in the field of palladium-catalyzed carbon dioxide utilization for the synthesis of high value added organic molecules. The review is structured on the basis of the kind of substrate undergoing the Pd-catalyzed carboxylation process. Accordingly, after the introductory section, the main sections of the review will illustrate Pd-catalyzed carboxylation of olefinic substrates, acetylenic substrates, and other substrates (aryl halides and triflates).


Introduction
The efficient incorporation of carbon dioxide into an organic substrate (carboxylation) under catalytic conditions to give high value added molecules is one of the most important and fascinating areas of current organic synthesis. In fact, carbon dioxide is a nonflammable, inexpensive and largely available C-1 feedstock. Moreover, the efficient conversion of CO 2 into organic compounds is a very attractive synthetic approach. In fact, it allows converting an important waste (it is well known that carbon dioxide is produced in enormous amounts from the combustion of fossil fuels for the production of energy) into a variety of useful compounds, which can find application as fuels or in the pharmaceutical or material fields. Accordingly, many efforts have been devoted by the scientific community to develop novel efficient and sustainable carboxylation methods, in particular under catalytic conditions, during the last years .
This short review is intended to present paradigmatic examples of carboxylation processes based on palladium catalysis, with particular emphasis to the more recently reported methods (coverage: from 1980ies to date). Only processes in which carbon dioxide is fully incorporated into the organic substrates will be considered, while the reactions in which CO 2 is incorporated as a carbonyl function only, resulting in indirect carbonylation rather than carboxylation, are beyond the scope of this review.

Palladium-Catalyzed Incorporation of Carbon Dioxide into Olefinic Substrates
Suitably functionalized olefins are excellent substrates for the Pd-catalyzed incorporation of carbon dioxide to give high value added heterocyclic compounds. For example, vinyl epoxides undergo a Pd(0)-promoted ring-opening process with formation of a πallylpalladium alkoxide intermediate I, which can attack CO 2 to give a π-allylpalladium carbonate II that then undergoes intramolecular nucleophilic attack to give vinyl-substituted 5-membered cyclic carbonates 1, as shown in Scheme 1. This kind of process was independently disclosed by the groups of Fujinami [35] and Trost [36,37] in the 1980s; an example of synthetic application is shown in Scheme 2 (in this and in all the following schemes of the review, unreactive ligands on palladium are not shown for clarity) [38].
In a similar manner, 5-vinyloxazolidinones 2 can be synthesized fro dines. For example, using a catalytic system consisting of Pd2(dba)3/PPh3/T tetrabutylammonium difluorotriphenylsilicate), in toluene as the solvent a ticularly mild reaction conditions (0 °C and atmospheric pressure of CO2), vinyloxazolidinones was prepared (Scheme 3). The process showed high r and was also diastereospecific [39]. Cycloalkylidenecyclopropanes, bearing the highly reactive cycloprop been reported to undergo ring-opening carboxylation under relatively mild yield five-membered lactones, as shown in Scheme 4 for the formation of Reactions were carried out in toluene at 120 °C under 40 atm of CO2, in th Pd2(dba)3/PCy3 as the catalytic system and dimethyl sulfoxide (DMSO) as reaction showed a certain degree of diastereoselectivity, favoring the forma astereoisomer with the carbonyl group in the axial position 3 in most cases. mechanism involves the initial oxidative insertion of Pd(0) into the cyclo with formation of a four-membered Pd(II) palladacycle intermediate I, Scheme 4, which may undergo a ring opening process to give a zwitterion dium complex II. The latter inserts CO2 by carbanion attack to give a carbox ionic intermediate III (only the intermediate leading to the major diast shown in the scheme), from which the final product 3 is formed by intramo of the carboxylate group to the -allyl moiety, with regeneration of the (Scheme 4).

Scheme 2. Synthesis of trans-(2-oxo-5-vinyl-1,3-dioxolan-4-yl)methyl 4-met
In a similar manner, 5-vinyloxazolidinones 2 can be synthes dines. For example, using a catalytic system consisting of Pd2(dba) tetrabutylammonium difluorotriphenylsilicate), in toluene as the so ticularly mild reaction conditions (0 °C and atmospheric pressure o vinyloxazolidinones was prepared (Scheme 3). The process showed and was also diastereospecific [39]. Cycloalkylidenecyclopropanes, bearing the highly reactive cy been reported to undergo ring-opening carboxylation under relativ yield five-membered lactones, as shown in Scheme 4 for the form Reactions were carried out in toluene at 120 °C under 40 atm of C Pd2(dba)3/PCy3 as the catalytic system and dimethyl sulfoxide (DM reaction showed a certain degree of diastereoselectivity, favoring th astereoisomer with the carbonyl group in the axial position 3 in mos mechanism involves the initial oxidative insertion of Pd(0) into t with formation of a four-membered Pd(II) palladacycle interme Scheme 4, which may undergo a ring opening process to give a zw dium complex II. The latter inserts CO2 by carbanion attack to give ionic intermediate III (only the intermediate leading to the maj shown in the scheme), from which the final product 3 is formed by In a similar manner, 5-vinyloxazolidinones 2 can be synthesized from vinylaziridines. For example, using a catalytic system consisting of Pd 2 (dba) 3 /PPh 3 /TBAT (TBAT = tetrabutylammonium difluorotriphenylsilicate), in toluene as the solvent and under particularly mild reaction conditions (0 • C and atmospheric pressure of CO 2 ), a variety of 5-vinyloxazolidinones was prepared (Scheme 3). The process showed high regioselectivity and was also diastereospecific [39].

Scheme 2. Synthesis of trans-(2-oxo-5-vinyl-1,3-dioxolan-4-yl)methyl 4-methy
In a similar manner, 5-vinyloxazolidinones 2 can be synthesiz dines. For example, using a catalytic system consisting of Pd2(dba)3/P tetrabutylammonium difluorotriphenylsilicate), in toluene as the solv ticularly mild reaction conditions (0 °C and atmospheric pressure of C vinyloxazolidinones was prepared (Scheme 3). The process showed h and was also diastereospecific [39]. Cycloalkylidenecyclopropanes, bearing the highly reactive cyclo been reported to undergo ring-opening carboxylation under relatively yield five-membered lactones, as shown in Scheme 4 for the formati Reactions were carried out in toluene at 120 °C under 40 atm of CO2 Pd2(dba)3/PCy3 as the catalytic system and dimethyl sulfoxide (DMS reaction showed a certain degree of diastereoselectivity, favoring the astereoisomer with the carbonyl group in the axial position 3 in most c mechanism involves the initial oxidative insertion of Pd(0) into the with formation of a four-membered Pd(II) palladacycle intermedi Scheme 4, which may undergo a ring opening process to give a zwit dium complex II. The latter inserts CO2 by carbanion attack to give a c ionic intermediate III (only the intermediate leading to the major shown in the scheme), from which the final product 3 is formed by in of the carboxylate group to the -allyl moiety, with regeneration o (Scheme 4). Cycloalkylidenecyclopropanes, bearing the highly reactive cyclopropane ring, have been reported to undergo ring-opening carboxylation under relatively mild conditions to yield five-membered lactones, as shown in Scheme 4 for the formation of 3 and 3 [40]. Reactions were carried out in toluene at 120 • C under 40 atm of CO 2 , in the presence of Pd 2 (dba) 3 /PCy 3 as the catalytic system and dimethyl sulfoxide (DMSO) as additive. The reaction showed a certain degree of diastereoselectivity, favoring the formation of the diastereoisomer with the carbonyl group in the axial position 3 in most cases. The proposed mechanism involves the initial oxidative insertion of Pd(0) into the cyclopropane ring with formation of a four-membered Pd(II) palladacycle intermediate I, as shown in Scheme 4, which may undergo a ring opening process to give a zwitterionic π-allypalladium complex II. The latter inserts CO 2 by carbanion attack to give a carboxylate zwitterionic intermediate III (only the intermediate leading to the major diastereoisomer is shown in the scheme), from which the final product 3 is formed by intramolecular attack of the carboxylate group to the π-allyl moiety, with regeneration of the Pd(0) catalyst (Scheme 4). Functionalized allylic substrates can also undergo carbon dioxide fixation unde Pd(0) catalysis. As an example, 2-(acetoxymethyl)-3-(trimethylsilyl)propenes were con verted into 2(5H)-furanones when allowed to react with CO2 (1 atm) in 1,2-dimethoxye thane (DME) or THF at 60-75 °C in the presence of Pd(PPh3)4, although in modest to mod erate isolated yields (35-62%), as exemplified in Scheme 5 for the formation of 4 [41] Mechanistically, the reaction follows a pathway similar to that seen in Scheme 1, as the key intermediate is a zwitterionic -allylpalladium complex I [formed by oxidative addi tion of the substrate to Pd(0)], which reacts with CO2 to give a zwitterionic carboxylate complex II. The latter undergoes cyclization (by intramolecular nucleophilic attack of the carboxylate to the -allylpalladium system), with regeneration of Pd(0) and formation o a 4-methylenedihydrofuran-2(3H)-one intermediate III, which eventually isomerizes to the final 2(5H)-furanone product 4 (Scheme 5). Vinyl-substituted 5-membered cyclic carbonates 5 were synthesized from allylic car bonates by a sequential CO2 elimination-fixation process, as shown in Scheme 6, with for mal CO2 recycling, again through the formation of a zwitterionic -allylpalladium com plex I [42]. Reactions were performed in the presence of Pd2(dba)3 as catalyst in the pres ence of dppf [1,1'-bis(diphenylphosphino)ferrocene] or dppe [1,2-bis(diphe nylphosphino)ethane] as ligand, in dioxane at 50 °C under inert atmosphere. The process was shown to be enantiospecific when starting from nonracemic allylic carbonates to yield nonracemic cyclic carbonates. Functionalized allylic substrates can also undergo carbon dioxide fixation under Pd(0) catalysis. As an example, 2-(acetoxymethyl)-3-(trimethylsilyl)propenes were converted into 2(5H)-furanones when allowed to react with CO 2 (1 atm) in 1,2-dimethoxyethane (DME) or THF at 60-75 • C in the presence of Pd(PPh 3 ) 4 , although in modest to moderate isolated yields (35-62%), as exemplified in Scheme 5 for the formation of 4 [41]. Mechanistically, the reaction follows a pathway similar to that seen in Scheme 1, as the key intermediate is a zwitterionic π-allylpalladium complex I [formed by oxidative addition of the substrate to Pd(0)], which reacts with CO 2 to give a zwitterionic carboxylate complex II. The latter undergoes cyclization (by intramolecular nucleophilic attack of the carboxylate to the π-allylpalladium system), with regeneration of Pd(0) and formation of a 4-methylenedihydrofuran-2(3H)one intermediate III, which eventually isomerizes to the final 2(5H)-furanone product 4 (Scheme 5). Functionalized allylic substrates can also undergo carbon dioxide fixation unde Pd(0) catalysis. As an example, 2-(acetoxymethyl)-3-(trimethylsilyl)propenes were con verted into 2(5H)-furanones when allowed to react with CO2 (1 atm) in 1,2-dimethoxye thane (DME) or THF at 60-75 °C in the presence of Pd(PPh3)4, although in modest to mod erate isolated yields (35-62%), as exemplified in Scheme 5 for the formation of 4 [41] Mechanistically, the reaction follows a pathway similar to that seen in Scheme 1, as th key intermediate is a zwitterionic -allylpalladium complex I [formed by oxidative addi tion of the substrate to Pd(0)], which reacts with CO2 to give a zwitterionic carboxylat complex II. The latter undergoes cyclization (by intramolecular nucleophilic attack of th carboxylate to the -allylpalladium system), with regeneration of Pd(0) and formation o a 4-methylenedihydrofuran-2(3H)-one intermediate III, which eventually isomerizes to the final 2(5H)-furanone product 4 (Scheme 5). Vinyl-substituted 5-membered cyclic carbonates 5 were synthesized from allylic car bonates by a sequential CO2 elimination-fixation process, as shown in Scheme 6, with for mal CO2 recycling, again through the formation of a zwitterionic -allylpalladium com plex I [42]. Reactions were performed in the presence of Pd2(dba)3 as catalyst in the pres ence of dppf [1,1'-bis(diphenylphosphino)ferrocene] or dppe [1,2-bis(diphe nylphosphino)ethane] as ligand, in dioxane at 50 °C under inert atmosphere. The proces was shown to be enantiospecific when starting from nonracemic allylic carbonates to yield nonracemic cyclic carbonates. Vinyl-substituted 5-membered cyclic carbonates 5 were synthesized from allylic carbonates by a sequential CO 2 elimination-fixation process, as shown in Scheme 6, with formal CO 2 recycling, again through the formation of a zwitterionic π-allylpalladium complex I [42]. Reactions were performed in the presence of Pd 2 (dba) 3 as catalyst in the presence of dppf [1,1 -bis(diphenylphosphino)ferrocene] or dppe [1,2-bis(diphenylphosphino)ethane] as ligand, in dioxane at 50 • C under inert atmosphere. The process was shown to be enantiospecific when starting from nonracemic allylic carbonates to yield nonracemic cyclic carbonates. In a subsequent work, the same research group reported the synthesis of dienylic 5membered cyclic carbonates 6 from 6-methoxycarbonyloxy-2,4-hexadien-1-ols under similar conditions [Pd2(dba)3 as catalyst in the presence of dppe or dppv (1,2-bis(diphenylphosphino)ethylene) as ligand, in dioxane at 50 °C], as shown in Scheme 7 [43]. Scheme 7. Synthesis of dienylic 5-membered cyclic carbonates 6 from 6-methoxycarbonyloxy-2,4hexadien-1-ols.
Allylamines have been reported to react with alkyl bromides and carbon dioxide (1 atm) in DMSO at room temperature, in the presence of Pd(PPh3)4 as catalyst and 1,5,7triazabicyclo[4.4.0]dec-5-ene (TBD) as base and under visible light irradiation (10 W blue LED lamp), to give 2-oxazolidinones 7 in good yields (Scheme 8) [44]. Experimental data were in agreement with a radical mechanism, which starts with the photoexcitation of Pd(0) followed by single electron transfer (SET) with the alkyl bromide to give a Pd(I) species I and an alkyl radical II. The latter reacts with the double bond of the carbamate intermediate III formed by the attack of the amino group of the allylamine substrate to CO2 in the presence of TBD, thus leading to a radical anion species IV. This species undergoes another SET process with Pd(I) with regeneration of the Pd(0) catalyst and formation of a zwitterionic intermediate V, whose cyclization by intramolecular nucleophilic attack finally affords the oxazolidinone product 7 (Scheme 8).  In a subsequent work, the same research group reported the synthesis of dienylic 5membered cyclic carbonates 6 from 6-methoxycarbonyloxy-2,4-hexadien-1-ols under similar conditions [Pd 2 (dba) 3 as catalyst in the presence of dppe or dppv (1,2-bis(diphenylphosphino) ethylene) as ligand, in dioxane at 50 • C], as shown in Scheme 7 [43]. In a subsequent work, the same research group reported the synthesis of dienylic 5membered cyclic carbonates 6 from 6-methoxycarbonyloxy-2,4-hexadien-1-ols under similar conditions [Pd2(dba)3 as catalyst in the presence of dppe or dppv (1,2-bis(diphenylphosphino)ethylene) as ligand, in dioxane at 50 °C], as shown in Scheme 7 [43]. Scheme 7. Synthesis of dienylic 5-membered cyclic carbonates 6 from 6-methoxycarbonyloxy-2,4hexadien-1-ols.
Allylamines have been reported to react with alkyl bromides and carbon dioxide (1 atm) in DMSO at room temperature, in the presence of Pd(PPh3)4 as catalyst and 1,5,7triazabicyclo[4.4.0]dec-5-ene (TBD) as base and under visible light irradiation (10 W blue LED lamp), to give 2-oxazolidinones 7 in good yields (Scheme 8) [44]. Experimental data were in agreement with a radical mechanism, which starts with the photoexcitation of Pd(0) followed by single electron transfer (SET) with the alkyl bromide to give a Pd(I) species I and an alkyl radical II. The latter reacts with the double bond of the carbamate intermediate III formed by the attack of the amino group of the allylamine substrate to CO2 in the presence of TBD, thus leading to a radical anion species IV. This species undergoes another SET process with Pd(I) with regeneration of the Pd(0) catalyst and formation of a zwitterionic intermediate V, whose cyclization by intramolecular nucleophilic attack finally affords the oxazolidinone product 7 (Scheme 8).   [44]. Experimental data were in agreement with a radical mechanism, which starts with the photoexcitation of Pd(0) followed by single electron transfer (SET) with the alkyl bromide to give a Pd(I) species I and an alkyl radical II. The latter reacts with the double bond of the carbamate intermediate III formed by the attack of the amino group of the allylamine substrate to CO 2 in the presence of TBD, thus leading to a radical anion species IV. This species undergoes another SET process with Pd(I) with regeneration of the Pd(0) catalyst and formation of a zwitterionic intermediate V, whose cyclization by intramolecular nucleophilic attack finally affords the oxazolidinone product 7 (Scheme 8). In a subsequent work, the same research group reported the synthesis of dienylic 5membered cyclic carbonates 6 from 6-methoxycarbonyloxy-2,4-hexadien-1-ols under similar conditions [Pd2(dba)3 as catalyst in the presence of dppe or dppv (1,2-bis(diphenylphosphino)ethylene) as ligand, in dioxane at 50 °C], as shown in Scheme 7 [43]. Scheme 7. Synthesis of dienylic 5-membered cyclic carbonates 6 from 6-methoxycarbonyloxy-2,4hexadien-1-ols.
Allylamines have been reported to react with alkyl bromides and carbon dioxide (1 atm) in DMSO at room temperature, in the presence of Pd(PPh3)4 as catalyst and 1,5,7triazabicyclo[4.4.0]dec-5-ene (TBD) as base and under visible light irradiation (10 W blue LED lamp), to give 2-oxazolidinones 7 in good yields (Scheme 8) [44]. Experimental data were in agreement with a radical mechanism, which starts with the photoexcitation of Pd(0) followed by single electron transfer (SET) with the alkyl bromide to give a Pd(I) species I and an alkyl radical II. The latter reacts with the double bond of the carbamate intermediate III formed by the attack of the amino group of the allylamine substrate to CO2 in the presence of TBD, thus leading to a radical anion species IV. This species undergoes another SET process with Pd(I) with regeneration of the Pd(0) catalyst and formation of a zwitterionic intermediate V, whose cyclization by intramolecular nucleophilic attack finally affords the oxazolidinone product 7 (Scheme 8). In a very similar manner, 1,4-dihydro-2H-3,1-benzoxazin-2-ones 8 were recently synthesized from 2-(1-arylvinyl)anilines, alkyl bromides, and carbon dioxide in the presence of the same catalyst [Pd(PPh 3 ) 4 ] and base (TBD) and under visible light irradiation (2 × 3 W blue LED lamps), at room temperature and under atmospheric pressure of CO 2 (Scheme 9) [45]. In a very similar manner, 1,4-dihydro-2H-3,1-benzoxazin-2-ones 8 were recently synthesized from 2-(1-arylvinyl)anilines, alkyl bromides, and carbon dioxide in the presence of the same catalyst [Pd(PPh3)4] and base (TBD) and under visible light irradiation (2  3 W blue LED lamps), at room temperature and under atmospheric pressure of CO2 (Scheme 9) [45]. Functionalized allenes are also useful substrate for Pd-catalyzed CO2 incorporation. As early as 1992, Tsuda and coworkers reported the dimerizative carboxylation of methoxyallene into (E)-6-methoxy-3-(methoxymethylene)-5-methylenetetrahydro-2H-pyran-2-one 9 (41% isolated yield), catalyzed by Pd2(dba)3 in the presence of Bu2PCH2CH2Py (Py = pyridyl) in MeCN as the solvent at 120 °C and under 50 kg/cm 2 pressure of carbon dioxide (Scheme 10) [46]. The methoxy substituent was essential to the success of the reaction.  More recently, aryloxyallenes have been reported to undergo a multicomponent reaction with amines, carbon dioxide, and aryl iodides, catalyzed by Pd(PPh3)4 in the presence of TBD, to give 1-aryloxy-2-arylallyl carbamates 10, according to Scheme 11 [47]. From a mechanistic point of view, the process is believed to begin with the oxidative addition of the aryl iodide to Pd(0) to give an ArPd(II) complex, which then inserts the allenyl moiety of the substrate thus leading to a -allylpalladium complex I. The final product is finally obtained by regioselective nucleophilic attack to the -allylpalladium moiety by the carbamate formed by the reaction between the amine and CO2 in the presence of TBD (Scheme 11). Scheme 11. Synthesis of 1-aryloxy-2-arylallyl carbamates 10 from aryloxyallenes, aryl iodides, and amines. Functionalized allenes are also useful substrate for Pd-catalyzed CO 2 incorporation. As early as 1992, Tsuda and coworkers reported the dimerizative carboxylation of methoxyallene into (E)-6-methoxy-3-(methoxymethylene)-5-methylenetetrahydro-2H-pyran-2-one 9 (41% isolated yield), catalyzed by Pd 2 (dba) 3 in the presence of Bu 2 PCH 2 CH 2 Py (Py = pyridyl) in MeCN as the solvent at 120 • C and under 50 kg/cm 2 pressure of carbon dioxide (Scheme 10) [46]. The methoxy substituent was essential to the success of the reaction. In a very similar manner, 1,4-dihydro-2H-3,1-benzoxazin-2-ones 8 were recently synthesized from 2-(1-arylvinyl)anilines, alkyl bromides, and carbon dioxide in the presence of the same catalyst [Pd(PPh3)4] and base (TBD) and under visible light irradiation (2  3 W blue LED lamps), at room temperature and under atmospheric pressure of CO2 (Scheme 9) [45]. Functionalized allenes are also useful substrate for Pd-catalyzed CO2 incorporation. As early as 1992, Tsuda and coworkers reported the dimerizative carboxylation of methoxyallene into (E)-6-methoxy-3-(methoxymethylene)-5-methylenetetrahydro-2H-pyran-2-one 9 (41% isolated yield), catalyzed by Pd2(dba)3 in the presence of Bu2PCH2CH2Py (Py = pyridyl) in MeCN as the solvent at 120 °C and under 50 kg/cm 2 pressure of carbon dioxide (Scheme 10) [46]. The methoxy substituent was essential to the success of the reaction. A palladacycle intermediate was proposed to be the key intermediate in product formation.
More recently, aryloxyallenes have been reported to undergo a multicomponent reaction with amines, carbon dioxide, and aryl iodides, catalyzed by Pd(PPh3)4 in the presence of TBD, to give 1-aryloxy-2-arylallyl carbamates 10, according to Scheme 11 [47]. From a mechanistic point of view, the process is believed to begin with the oxidative addition of the aryl iodide to Pd(0) to give an ArPd(II) complex, which then inserts the allenyl moiety of the substrate thus leading to a -allylpalladium complex I. The final product is finally obtained by regioselective nucleophilic attack to the -allylpalladium moiety by the carbamate formed by the reaction between the amine and CO2 in the presence of TBD (Scheme 11). Scheme 11. Synthesis of 1-aryloxy-2-arylallyl carbamates 10 from aryloxyallenes, aryl iodides, and amines. Scheme 10. Synthesis of (E)-6-methoxy-3-(methoxymethylene)-5-methylenetetrahydro-2H-pyran-2one 9 from methoxyallene.
More recently, aryloxyallenes have been reported to undergo a multicomponent reaction with amines, carbon dioxide, and aryl iodides, catalyzed by Pd(PPh 3 ) 4 in the presence of TBD, to give 1-aryloxy-2-arylallyl carbamates 10, according to Scheme 11 [47]. From a mechanistic point of view, the process is believed to begin with the oxidative addition of the aryl iodide to Pd(0) to give an ArPd(II) complex, which then inserts the allenyl moiety of the substrate thus leading to a π-allylpalladium complex I. The final product is finally obtained by regioselective nucleophilic attack to the π-allylpalladium moiety by the carbamate formed by the reaction between the amine and CO 2 in the presence of TBD (Scheme 11). In a very similar manner, 1,4-dihydro-2H-3,1-benzoxazin-2-ones 8 were recently synthesized from 2-(1-arylvinyl)anilines, alkyl bromides, and carbon dioxide in the presence of the same catalyst [Pd(PPh3)4] and base (TBD) and under visible light irradiation (2  3 W blue LED lamps), at room temperature and under atmospheric pressure of CO2 (Scheme 9) [45]. Functionalized allenes are also useful substrate for Pd-catalyzed CO2 incorporation. As early as 1992, Tsuda and coworkers reported the dimerizative carboxylation of methoxyallene into (E)-6-methoxy-3-(methoxymethylene)-5-methylenetetrahydro-2H-pyran-2-one 9 (41% isolated yield), catalyzed by Pd2(dba)3 in the presence of Bu2PCH2CH2Py (Py = pyridyl) in MeCN as the solvent at 120 °C and under 50 kg/cm 2 pressure of carbon dioxide (Scheme 10) [46]. The methoxy substituent was essential to the success of the reaction. A palladacycle intermediate was proposed to be the key intermediate in product formation.
More recently, aryloxyallenes have been reported to undergo a multicomponent reaction with amines, carbon dioxide, and aryl iodides, catalyzed by Pd(PPh3)4 in the presence of TBD, to give 1-aryloxy-2-arylallyl carbamates 10, according to Scheme 11 [47]. From a mechanistic point of view, the process is believed to begin with the oxidative addition of the aryl iodide to Pd(0) to give an ArPd(II) complex, which then inserts the allenyl moiety of the substrate thus leading to a -allylpalladium complex I. The final product is finally obtained by regioselective nucleophilic attack to the -allylpalladium moiety by the carbamate formed by the reaction between the amine and CO2 in the presence of TBD (Scheme 11). Scheme 11. Synthesis of 1-aryloxy-2-arylallyl carbamates 10 from aryloxyallenes, aryl iodides, and amines. Scheme 11. Synthesis of 1-aryloxy-2-arylallyl carbamates 10 from aryloxyallenes, aryl iodides, and amines.
When the aryloxy and Ar-I functional groups were present in the same substrate in relative ortho positions, 3-methylene-2,3-dihydrobenzofuran-2-yl carbamates 11 were obtained by a similar sequence of mechanistic steps, the carbamate nucleophilic attack to the -allyl system occurring in this case intramolecularly (Scheme 12) [48]. Interestingly, (1-tosyl-1H-indol-3-yl)methyl carbamates were selectively formed when starting from 2-iodo-N-(propa-1,2-dien-1-yl)-N-tosylanilines, by an inversion of regiochemistry in the intramolecular nucleophilic attack, probably owing to the steric hindrance exerted by the tosyl group on nitrogen. Ikayara and coworkers reported the reaction of -allenyl amines with dense CO2 (11.5 MPa) to give 5-vinyl-2-oxazolidinones 13 under the catalysis of Pd(0), obtained in situ from palladium acetate, as shown in Scheme 14 [50]. The proposed mechanism starts with the formation of a carbamate intermediate I (from the reaction between the substrate and CO2) followed by oxidative addition of the -OH group to Pd(0). Insertion of the internal allenyl double bond into the ensuing Pd-H bond then takes place, with formation of a -allylpalladium complex II. Cyclization with reductive elimination of Pd(0) finally yields the oxazolidinone product 13 (Scheme 14). Ikayara and coworkers reported the reaction of α-allenyl amines with dense CO 2 (11.5 MPa) to give 5-vinyl-2-oxazolidinones 13 under the catalysis of Pd(0), obtained in situ from palladium acetate, as shown in Scheme 14 [50]. The proposed mechanism starts with the formation of a carbamate intermediate I (from the reaction between the substrate and CO 2 ) followed by oxidative addition of the -OH group to Pd(0). Insertion of the internal allenyl double bond into the ensuing Pd-H bond then takes place, with formation of a π-allylpalladium complex II. Cyclization with reductive elimination of Pd(0) finally yields the oxazolidinone product 13 (Scheme 14). In 1999, Inoue and coworkers reported the Pd(0)-catalyzed formation of vinyl-substituted cyclic carbonates from 2,3-dienols or 3,4-dienols, aryl or vinyl halides, and CO2, as exemplified in Scheme 15 for the synthesis of 4-vinyl-1,3-dioxolan-2-ones 14 from 2,3dienols and aryl halides [51]. The process, carried out in DMA (N,N-dimethylacetamide) at 50100 °C under 40 atm of CO2, in the presence of Pd(PPh3)4 as catalyst and K2CO3 as base, took place through oxidative addition of the halide to Pd(0), followed by insertion of the allenyl moiety of the deprotonated substrate to give a -allylpalladium complex I. The final product 14 was then formed by attack of the anionic oxygen to CO2 followed by intramolecular nucleophilic attack of the ensuing carbonate moiety to the -allylpalladium system, with regeneration of Pd(0) (Scheme 15). In 1999, Inoue and coworkers reported the Pd(0)-catalyzed formation of vinyl-substituted cyclic carbonates from 2,3-dienols or 3,4-dienols, aryl or vinyl halides, and CO 2 , as exemplified in Scheme 15 for the synthesis of 4-vinyl-1,3-dioxolan-2-ones 14 from 2,3-dienols and aryl halides [51]. The process, carried out in DMA (N,N-dimethylacetamide) at 50-100 • C under 40 atm of CO 2 , in the presence of Pd(PPh 3 ) 4 as catalyst and K 2 CO 3 as base, took place through oxidative addition of the halide to Pd(0), followed by insertion of the allenyl moiety of the deprotonated substrate to give a π-allylpalladium complex I. The final product 14 was then formed by attack of the anionic oxygen to CO 2 followed by intramolecular nucleophilic attack of the ensuing carbonate moiety to the π-allylpalladium system, with regeneration of Pd(0) (Scheme 15). In 1999, Inoue and coworkers reported the Pd(0)-catalyzed formation of vi stituted cyclic carbonates from 2,3-dienols or 3,4-dienols, aryl or vinyl halides, a as exemplified in Scheme 15 for the synthesis of 4-vinyl-1,3-dioxolan-2-ones 14 f dienols and aryl halides [51]. The process, carried out in DMA (N,N-dimethylace at 50100 °C under 40 atm of CO2, in the presence of Pd(PPh3)4 as catalyst and K base, took place through oxidative addition of the halide to Pd(0), followed by i of the allenyl moiety of the deprotonated substrate to give a -allylpalladium co The final product 14 was then formed by attack of the anionic oxygen to CO2 follo intramolecular nucleophilic attack of the ensuing carbonate moiety to the -al dium system, with regeneration of Pd(0) (Scheme 15). In a similar way, 5-vinyl-2-oxazolidinones 15 were synthesized from 2,3-allenyl amines, aryl iodides and CO 2 (1 atm) in the presence of Pd(PPh 3 ) 4 and K 2 CO 3 as the base, in DMSO at 70 • C (Scheme 16) [52]. The reaction starts with the oxidative addition of the aryl iodide to Pd(0) to give an Ar-Pd-I complex, which inserts the allenyl moiety of the π-allylpalladium carbamate intermediate I formed by the reaction between the allenyl amine and CO 2 . Intramolecular nucleophilic attack of the carbamate to the πallylpalladium moiety eventually leads to the vinyloxazolidinone product 15 with re-generation of Pd(0) (Scheme 16). Interestingly, the use of the ligand Gorlos-Phos•HBF 4 (Gorlos-Phos = dicyclohexyl(2,6-diisopropoxyphenyl)phosphane) allowed a stereoselective synthesis of (Z)-5-alkenyloxazolidin-2-ones when starting from 4-monosubstituted 2,3-allenyl amines [53]. Conjugate dienes are also reactive toward carbon dioxide under palladium catal Following the pioneering studies performed by the groups of Inoue [54,55] and M [56,57], in 1983 Behr and coworkers reported the reaction of 1,3-butadiene with CO2 ried out in the presence of Pd(acac)2 as the palladium source (0.18%) and i Pr3P as lig in acetonitrile at 90 °C, to give 3-ethylidene-6-vinyltetrahydro-2H-pyran-2-one (or 2-e idene-6-hepten-5-olide, EVL) 16 in 38% isolated yield and a TON (Turnover Numbe ca. 310 mol of product per mol of palladium used (Scheme 17) [58,59]. Interestingly 6-membered lactone could be isomerized into the corresponding 5-membered on ethyl-5-propylidenefuran-2(5H)-one, 17% GLC yield] under the same reaction condit but with a higher catalyst loading (1.19%) [59]. EVL is a useful precursor for the prep tion of different high value added products [60][61][62][63][64], including polymers [62][63][64], suc high molecular weight polymers with a carbon dioxide content of 33 mol%, obtaine the -lactone free-radical polymerization [64]. Mechanistically, the telomerization pro leading to EVL was believed to occur through the formation of a bis--allylpallad complex I [from the reaction between butadiene and Pd(0)], followed by CO2 inse and cyclization with reductive elimination of Pd(0) (Scheme 17). Conjugate dienes are also reactive toward carbon dioxide under palladium catalysis. Following the pioneering studies performed by the groups of Inoue [54,55] and Musco [56,57], in 1983 Behr and coworkers reported the reaction of 1,3-butadiene with CO 2 carried out in the presence of Pd(acac) 2 as the palladium source (0.18%) and i Pr 3 P as ligand, in acetonitrile at 90 • C, to give 3-ethylidene-6-vinyltetrahydro-2H-pyran-2-one (or 2-ethylidene-6-hepten-5-olide, EVL) 16 in 38% isolated yield and a TON (Turnover Number) of ca. 310 mol of product per mol of palladium used (Scheme 17) [58,59]. Interestingly, this 6-membered lactone could be isomerized into the corresponding 5-membered one [3-ethyl-5-propylidenefuran-2(5H)-one, 17% GLC yield] under the same reaction conditions, but with a higher catalyst loading (1.19%) [59]. EVL is a useful precursor for the preparation of different high value added products [60][61][62][63][64], including polymers [62][63][64], such as high molecular weight polymers with a carbon dioxide content of 33 mol%, obtained by the δ-lactone free-radical polymerization [64]. Mechanistically, the telomerization process leading to EVL was believed to occur through the formation of a bis-π-allylpalladium complex I [from the reaction between butadiene and Pd(0)], followed by CO 2 insertion and cyclization with reductive elimination of Pd(0) (Scheme 17). Conjugate dienes are also reactive toward carbon dioxide under pallad Following the pioneering studies performed by the groups of Inoue [54,5 [56,57], in 1983 Behr and coworkers reported the reaction of 1,3-butadiene ried out in the presence of Pd(acac)2 as the palladium source (0.18%) and i P in acetonitrile at 90 °C, to give 3-ethylidene-6-vinyltetrahydro-2H-pyran-2-o idene-6-hepten-5-olide, EVL) 16 in 38% isolated yield and a TON (Turnov ca. 310 mol of product per mol of palladium used (Scheme 17) [58,59]. Inte 6-membered lactone could be isomerized into the corresponding 5-mem ethyl-5-propylidenefuran-2(5H)-one, 17% GLC yield] under the same reacti but with a higher catalyst loading (1.19%) [59]. EVL is a useful precursor fo tion of different high value added products [60][61][62][63][64], including polymers [6 high molecular weight polymers with a carbon dioxide content of 33 mol% the -lactone free-radical polymerization [64]. Mechanistically, the telomeri leading to EVL was believed to occur through the formation of a bis--a complex I [from the reaction between butadiene and Pd(0)], followed by and cyclization with reductive elimination of Pd(0) (Scheme 17). The process was later studied by Dinjus and Leitner [65], among others [66][67][68][69], who were able for the first time to isolate and characterize by NMR the mixture of isomeric lactones [6-(prop-1-en-2-yl)-3-(propan-2-ylidene)tetrahydro-2H-pyran-2-one and 6-methyl-3-(propan-2-ylidene)-6-vinyltetrahydro-2H-pyran-2-one] obtained from isoprene [65]. These studies evidenced the importance of the use of a hindered phosphine ligand as well as of a nitrile solvent for the success of the reaction.

Palladium-Catalyzed Incorporation of Carbon Dioxide into Acetylenic Substrates
Acetylenic substrates have been reported to undergo several important carboxylation processes catalyzed by palladium, with formation of high value added compounds.

Palladium-Catalyzed Incorporation of Carbon Dioxide into Acetylenic
Acetylenic substrates have been reported to undergo several important processes catalyzed by palladium, with formation of high value added com In 1986, Utimoto and coworkers reported the Pd(II)-catalyzed reactio alkynyl carbonates (obtained from the reaction between lithium 2-alkyn CO2) with allylic chlorides to give 4-(but-3-en-1-ylidene)-1,3-dioxolan-2-on 18) [76]. The synthetic transformation was carried out in a one-pot, two-st allowing ynolate to react with CO2 first (in THF at -78 °C) and then adding ride together with the catalyst PdCl2(MeCN)2 at the same temperature follow at 0 °C for 4 h, as shown in Scheme 18. Later on, Inoue and coworkers reported the Pd(0)-catalyzed reaction between sodium 2-alkyn-1-olates bearing a terminal triple bond, aryl halides, and CO 2 to give cyclic carbonates 18 [(E)-4-(arylmethylene)-1,3-dioxolan-2-ones], as shown in Scheme 19 [77]. Reactions were carried out under 10 atm of CO 2 , in THF at 100 • C and in the presence of 2 mol% of Pd(PPh 3 ) 4 . In this process, the initial oxidative addition of the aryl halide to Pd(0) leads to an Ar-Pd-X complex, which electrophilically activates the triple bond toward the anti 5-exo-dig intramolecular nucleophilic attack by the carbonate anion I formed by the reaction between the ynolate and CO 2 (Scheme 19). 2-Ynolates can also be formed in situ starting by deprotonation of propargyl alcohols in the presence of a suitable base. For example, recently a variety of propargyl alcohols with the triple bond substituted with an aryl group were converted into 5-(diarylmethylene)-1,3-dioxolan-2-ones 19 by their Pd(0)-catalyzed reaction with aryl halides and CO2 (1 atm), carried out in the presence of Pd2(dba)3 as catalyst and t BuOLi as the base (Scheme 20) [78]. Interestingly, with substrates bearing a terminal triple bond, a sequential Sonogashira coupling-carboxylation process took place, as exemplified in Scheme 20 for the case of the reaction of 2-methylbut-3-yn-2-ol with PhI (3 equiv) and CO2. The reaction, carried out in the presence of 5 mol% of PdCl2(PPh3)2 as the catalyst precursor, CuI (10 mol%) as cocatalyst, and t BuOLi as base (3 equiv), led to formation of 5-(diphenylmethylene)-4,4-dimethyl-1,3-dioxolan-2-one 20 in 55% yield (Scheme 20). Polymeric materials can be obtained starting from bis(propargylic alcohol)s and aryl dihalides. Thus, linear and hyperbranched five-membered cyclic carbonate-based polymers 21 with high weight-average molecular weights (up to 42,500, 96% yield) were recently produced by allowing to react bis(propargylic alcohol) monomers and aryl dihalide monomers with CO2 (1 atm) in DMF in the presence of Pd(OAc)2 as catalyst precursor and t BuOLi as the base (Scheme 21) [79]. 2-Ynolates can also be formed in situ starting by deprotonation of propargyl alcohols in the presence of a suitable base. For example, recently a variety of propargyl alcohols with the triple bond substituted with an aryl group were converted into 5-(diarylmethylene)-1,3-dioxolan-2-ones 19 by their Pd(0)-catalyzed reaction with aryl halides and CO 2 (1 atm), carried out in the presence of Pd 2 (dba) 3 as catalyst and t BuOLi as the base (Scheme 20) [78]. Interestingly, with substrates bearing a terminal triple bond, a sequential Sonogashira coupling-carboxylation process took place, as exemplified in Scheme 20 for the case of the reaction of 2-methylbut-3-yn-2-ol with PhI (3 equiv) and CO 2 . The reaction, carried out in the presence of 5 mol% of PdCl 2 (PPh 3 ) 2 as the catalyst precursor, CuI (10 mol%) as cocatalyst, and t BuOLi as base (3 equiv), led to formation of 5-(diphenylmethylene)-4,4dimethyl-1,3-dioxolan-2-one 20 in 55% yield (Scheme 20).
2-Ynolates can also be formed in situ starting by deprotonation of p in the presence of a suitable base. For example, recently a variety of pr with the triple bond substituted with an aryl group were converte methylene)-1,3-dioxolan-2-ones 19 by their Pd(0)-catalyzed reaction with CO2 (1 atm), carried out in the presence of Pd2(dba)3 as catalyst and t B (Scheme 20) [78]. Interestingly, with substrates bearing a terminal triple b Sonogashira coupling-carboxylation process took place, as exemplified the case of the reaction of 2-methylbut-3-yn-2-ol with PhI (3 equiv) and C carried out in the presence of 5 mol% of PdCl2(PPh3)2 as the catalyst p mol%) as cocatalyst, and t BuOLi as base (3 equiv), led to formation methylene)-4,4-dimethyl-1,3-dioxolan-2-one 20 in 55% yield (Scheme 20 Polymeric materials can be obtained starting from bis(propargylic alcohol)s and aryl dihalides. Thus, linear and hyperbranched five-membered cyclic carbonate-based polymers 21 with high weight-average molecular weights (up to 42,500, 96% yield) were recently produced by allowing to react bis(propargylic alcohol) monomers and aryl dihalide monomers with CO 2 (1 atm) in DMF in the presence of Pd(OAc) 2 as catalyst precursor and t BuOLi as the base (Scheme 21) [79]. With propargylic substrates bearing a potential leaving group, Pd-catalyzed CO quential elimination-fixation may occur through the formation of -propargylpallad species, in a similar way as seen in Section 2 for allylic carbonates (Schemes 6 and 7) Thus, in 2001, Yoshida and Hihara reported the synthesis of aryloxyvinyl-substitut membered cyclic carbonates 22 by the reaction of 4-hydroxy-2-yn-1-yl methyl carbon with phenols, carried out in the presence of Pd2(dba)3 and dppe in dioxane at 25-5 (Scheme 22) [81]. Higher product yields were obtained by performing the reaction u 1 atm of CO2 [81][82][83]. The reaction was also shown to be enantioselective (ees up to in the presence of the nonracemic ligand (S)-BINAP [82] and enantiospecific (with ch ity transfer) when starting from nonracemic substrates [83]. The process begins wit reaction between the substrate and Pd(0) to give carbon dioxide and -propargylp dium methoxide complex I. The latter then undergoes nucleophilic attack by phenol ing to a -allylpalladium intermediate II, from which the final product is formed by a to CO2 followed by intramolecular nucleophilic attack of the ensuing carbonate to t allylpalladium moiety (Scheme 22). With propargylic substrates bearing a potential leaving group, Pd-catalyzed CO 2 sequential elimination-fixation may occur through the formation of π-propargylpalladium species, in a similar way as seen in Section 2 for allylic carbonates (Schemes 6 and 7) [80]. Thus, in 2001, Yoshida and Hihara reported the synthesis of aryloxyvinyl-substituted 5membered cyclic carbonates 22 by the reaction of 4-hydroxy-2-yn-1-yl methyl carbonates with phenols, carried out in the presence of Pd 2 (dba) 3 and dppe in dioxane at 25-50 • C (Scheme 22) [81]. Higher product yields were obtained by performing the reaction under 1 atm of CO 2 [81][82][83]. The reaction was also shown to be enantioselective (ees up to 93%) in the presence of the nonracemic ligand (S)-BINAP [82] and enantiospecific (with chirality transfer) when starting from nonracemic substrates [83]. The process begins with the reaction between the substrate and Pd(0) to give carbon dioxide and π-propargylpalladium methoxide complex I. The latter then undergoes nucleophilic attack by phenol leading to a π-allylpalladium intermediate II, from which the final product is formed by attack to CO 2 followed by intramolecular nucleophilic attack of the ensuing carbonate to the π-allylpalladium moiety (Scheme 22).

Scheme 21.
Formation of five-membered cyclic carbonate-based polymers 21 from bis(pro alcohol)s and aryl dihalides.
With propargylic substrates bearing a potential leaving group, Pd-catalyzed quential elimination-fixation may occur through the formation of -propargylpa species, in a similar way as seen in Section 2 for allylic carbonates (Schemes 6 and Thus, in 2001, Yoshida and Hihara reported the synthesis of aryloxyvinyl-substi membered cyclic carbonates 22 by the reaction of 4-hydroxy-2-yn-1-yl methyl car with phenols, carried out in the presence of Pd2(dba)3 and dppe in dioxane at 2 (Scheme 22) [81]. Higher product yields were obtained by performing the reactio 1 atm of CO2 [81][82][83]. The reaction was also shown to be enantioselective (ees up in the presence of the nonracemic ligand (S)-BINAP [82] and enantiospecific (wit ity transfer) when starting from nonracemic substrates [83]. The process begins w reaction between the substrate and Pd(0) to give carbon dioxide and -proparg dium methoxide complex I. The latter then undergoes nucleophilic attack by phen ing to a -allylpalladium intermediate II, from which the final product is formed b to CO2 followed by intramolecular nucleophilic attack of the ensuing carbonate t allylpalladium moiety (Scheme 22). More recently, some propargylic epoxides with internal triple bond (trans-1-ethynyl-7-oxabicyclo[4.1.0]heptanes, in particular) were also used as substrates under similar conditions, with the addition of 3A molecular sieves (MS) (presumably to avoid substrate ring opening by water) and under 1 atm of CO 2 (Scheme 23) [84]. The reaction, leading to 2-substituted (1-aryloxyvinyl)hexahydrobenzo[d] [1,3]dioxol-2-ones 23 in modest to good yields, took place through the same kind of mechanistic route seen above for propargylic carbonates (Scheme 22), the key π-propargylpalladium zwitterionic complex I being this time formed by Pd(0)-promoted epoxide ring opening through an anti S N 2'-type attack (Scheme 23).
Molecules 2021, 26, x 12 time formed by Pd(0)-promoted epoxide ring opening through an anti SN2'-type at (Scheme 23). Propargyl amines are excellent substrates for the Pd-catalyzed CO2 incorporatio give high value added oxazolidinone derivatives. In 1997, our research group repo the first example of catalytic sequential incorporation of both carbon oxides (carbon d ide and carbon monoxide) into an organic substrate, ,'-disubstutited propargylam in particular [85]. The process was catalyzed by Pd(II) and took place in the presenc PdI2 (1 mol%), KI, MeOH (also used as solvent) at 50 °C for 25-65 h, under 50 atm 8:1:1 mixture of CO2-CO-air, to give mixtures of 5-(methoxycarbonylmethylene)oxa din-2-ones 24 (with Z configuration of the double bond) and 24' (with E configura around the exocyclic double bond) in 80-90% total yields (Z/E ratio from 2:1 to (Scheme 24) [85,86]. Overall, the reaction corresponded to an oxidative carbonyla [87][88][89][90][91][92][93][94][95][96][97][98][99] of the carbamate species initially formed by nitrogen attack to CO2, with oxy (from air) as the external oxidant and with formation of water as benign coproduct. M specifically, the anionic carbamate I (formed from the reaction between the proparg mine substrate and CO2) led to the main product, (Z)-5-(methoxycarbonylmethylene azolidin-2-one 24, through the formation of a palladium carbamate complex II, follo by intramolecular syn 5-exo-dig insertion of the triple bond to give III, CO insertion to and nucleophilic displacement by MeOH (Scheme 24, path a) [85,86]. On the other h intermediate I could also undergo anti 5-exo-dig nucleophilic attack of the anionic ca mate moiety to the triple bond coordinated to Pd(II), leading to an E-vinylpalladium c plex V. Carbon monoxide insertion then took place, with formation of an E-acylpallad intermediate VI, from which the final (E)-5-(methoxycarbonylmethylene)oxazolid one 24' was formed by nucleophilic displacement by MeOH (Scheme 24, path b). In e case, Pd(0) was formed together with the organic products. The overall process bec catalytic thanks to a very efficient reoxidation of Pd(0) to Pd(II), involving the initial dation of 2 mol of HI (also formed during the reaction) by oxygen (from air) to prod iodine, followed by the oxidative addition of I2 to Pd(0) to give back PdI2 (Scheme Propargyl amines are excellent substrates for the Pd-catalyzed CO 2 incorporation to give high value added oxazolidinone derivatives. In 1997, our research group reported the first example of catalytic sequential incorporation of both carbon oxides (carbon dioxide and carbon monoxide) into an organic substrate, α,α'-disubstutited propargylamines in particular [85]. The process was catalyzed by Pd(II) and took place in the presence of PdI 2 (1 mol%), KI, MeOH (also used as solvent) at 50 • C for 25-65 h, under 50 atm of a 8:1:1 mixture of CO 2 -CO-air, to give mixtures of 5-(methoxycarbonylmethylene)oxazolidin-2ones 24 (with Z configuration of the double bond) and 24 (with E configuration around the exocyclic double bond) in 80-90% total yields (Z/E ratio from 2:1 to 3:1) (Scheme 24) [85,86]. Overall, the reaction corresponded to an oxidative carbonylation [87][88][89][90][91][92][93][94][95][96][97][98][99] of the carbamate species initially formed by nitrogen attack to CO 2 , with oxygen (from air) as the external oxidant and with formation of water as benign coproduct. More specifically, the anionic carbamate I (formed from the reaction between the propargylamine substrate and CO 2 ) led to the main product, (Z)-5-(methoxycarbonylmethylene)oxazolidin-2-one 24, through the formation of a palladium carbamate complex II, followed by intramolecular syn 5-exo-dig insertion of the triple bond to give III, CO insertion to IV, and nucleophilic displacement by MeOH (Scheme 24, path a) [85,86]. On the other hand, intermediate I could also undergo anti 5-exo-dig nucleophilic attack of the anionic carbamate moiety to the triple bond coordinated to Pd(II), leading to an E-vinylpalladium complex V. Carbon monoxide insertion then took place, with formation of an E-acylpalladium intermediate VI, from which the final (E)-5-(methoxycarbonylmethylene)oxazolidin-2-one 24 was formed by nucleophilic displacement by MeOH (Scheme 24, path b). In either case, Pd(0) was formed together with the organic products. The overall process became catalytic thanks to a very efficient reoxidation of Pd(0) to Pd(II), involving the initial oxidation of 2 mol of HI (also formed during the reaction) by oxygen (from air) to produce iodine, followed by the oxidative addition of I 2 to Pd(0) to give back PdI 2 (Scheme 24) [100,101]. This sequential carboxylation-oxidative alkoxycarbonylation of propargyl amines to 5-(methoxycarbonylmethylene)oxazolidin-2-ones still today represents the only example reported in the literature of Pd(II)-catalyzed incorporation of both CO 2 and CO into an organic substrate.
The Pd-catalyzed incorporation of CO 2 alone (without CO) into propargylic amines has also been reported. Thus, in 2002, Shi and Shen published the Pd(II)-catalyzed carboxylation of these substrates under 40 Kg/cm 2 of CO 2 to give methyleneoxazolidinones 25, using Pd(OAc) 2 as catalyst precursor, in toluene as the solvent at 50 • C for 48 h (Scheme 25) [102]. Products were possibly formed through mechanistic pathways similar to those seen before in Scheme 24, as shown in Scheme 25. More recently, it was reported the use of an indenediide palladium complex as efficient catalyst for promoting this kind of transformation with a variety of differently substituted substrates (including propargyl amines bearing an internal triple bond), under mild condi-tions (0.5-1 bar of CO 2 , 40-80 • C in DMSO as the solvent), although with a higher catalyst loading (1-5 mol%) (Scheme 26) [103]. The Z configuration around the exocyclic double bond, observed for the 5-alkylideneoxazolidin-2-ones 26 obtained from propargyl amines with internal triple bond, was compatible with the anti 5-exo-dig cyclization pathway, as shown in Scheme 26. Detailed DFT investigations allowed identifying the cyclization step as the rate-determining step of the process. In a similar manner, more recently 5-arylideneoxazolidine-2,4-diones 28 were synthesized starting from propargylic amides, aryl halides, and CO2, in the presence of In a similar manner, more recently 5-arylideneoxazolidine-2,4-diones 28 were synthesized starting from propargylic amides, aryl halides, and CO2, in the presence of In a similar manner, more recently 5-arylideneoxazolidine-2,4-diones 28 were synthesized starting from propargylic amides, aryl halides, and CO 2 , in the presence of PdCl 2 (PPh 3 ) 2 as the catalytic precursor, CuI as cocatalyst, and potassium carbonate as base (Scheme 28) [105]. The role of CuI was believed to be related to the possible stabilization of the carbamate intermediate I (by chelation of the amide carbonyl and the carboxylate group, leading to complex II), which avoids protonolysis, leading to oxazolidinones not incorporating the aryl moiety.

Palladium-Catalyzed Incorporation of Carbon Dioxide into Other Substrates
Under suitable conditions, aryl halides and triflates can undergo palladium-catalyzed carboxylation with formation of important compounds.
In 2017, the groups of Maes and Beller reported the Pd(0)-catalyzed reaction of 2bromoanilines with CO2 and isocyanides to give quinazoline-1,4(1H,3H)-diones 29 [106]. Reactions were performed in the presence of Pd(OAc)2 as the catalyst precursor, in the presence of BuPdAd2 (Ad = adamantly) as ligand and Cs2CO3 as base, in dioxane as the solvent at 80 °C and under 10 bar of CO2 (Scheme 29). In the simplified version of the mechanism, oxidative addition of the Ar-Br bond to Pd(0) takes place, followed by insertion of the isocyanide. The reaction of the amino group with CO2 in the presence of the base then leads to a palladium carbamate intermediate I, which undergoes reductive elimination to yield Pd(0) and a 4-imino-1,4-dihydro-2H-benzo[d] [1,3]oxazin-2-one intermediate II, from which the final product is obtained by base-promoted rearrangement (Scheme 29). Scheme 28. Synthesis of 5-arylideneoxazolidin-2,4-diones 28 from propargyl amides and aryl iodides.

Palladium-Catalyzed Incorporation of Carbon Dioxide into Other Substrates
Under suitable conditions, aryl halides and triflates can undergo palladium-catalyzed carboxylation with formation of important compounds.
In 2017, the groups of Maes and Beller reported the Pd(0)-catalyzed reaction of 2bromoanilines with CO 2 and isocyanides to give quinazoline-1,4(1H,3H)-diones 29 [106]. Reactions were performed in the presence of Pd(OAc) 2 as the catalyst precursor, in the presence of BuPdAd 2 (Ad = adamantly) as ligand and Cs 2 CO 3 as base, in dioxane as the solvent at 80 • C and under 10 bar of CO 2 (Scheme 29). In the simplified version of the mechanism, oxidative addition of the Ar-Br bond to Pd(0) takes place, followed by insertion of the isocyanide. The reaction of the amino group with CO 2 in the presence of the base then leads to a palladium carbamate intermediate I, which undergoes reductive elimination to yield Pd(0) and a 4-imino-1,4-dihydro-2H-benzo[d] [1,3]oxazin-2-one intermediate II, from which the final product is obtained by base-promoted rearrangement (Scheme 29). Interestingly, very recently this kind of reactivity has been exploited fo of new heterocyclic polymers 30 with self-assembly and sensing properties bis(2-iodoaniline) and diisocyanide monomers, using PdCl2 and PPh3 as th cursor, under 1 atm of CO2, in DMA at 80 °C for 18 h (Scheme 32) [109]. Interestingly, very recently this kind of reactivity has been exploited fo of new heterocyclic polymers 30 with self-assembly and sensing properties bis(2-iodoaniline) and diisocyanide monomers, using PdCl2 and PPh3 as th cursor, under 1 atm of CO2, in DMA at 80 °C for 18 h (Scheme 32) [109]. Interestingly, very recently this kind of reactivity has been exploited for the synthesis of new heterocyclic polymers 30 with self-assembly and sensing properties, starting from bis(2iodoaniline) and diisocyanide monomers, using PdCl 2 and PPh 3 as the catalyst precursor, under 1 atm of CO 2 , in DMA at 80 • C for 18 h (Scheme 32) [109]. Palladium-catalyzed incorporation of CO and CO2 into 2-iodoanilines to giv anhydrides 31 has also been reported [110]. Reactions were carried out in THF under 1 MPa of CO2 and 0.5 MPa of CO, in the presence of Pd(PPh3)4 as cata AcOCs as base (Scheme 33). Mechanistically, the process is similar to that seen in 29, with CO in place of the isocyanide (and without the final rearrangement step) ( 33). Palladium-catalyzed incorporation of CO and CO 2 into 2-iodoanilines to give isatoic anhydrides 31 has also been reported [110]. Reactions were carried out in THF at 60 • C under 1 MPa of CO 2 and 0.5 MPa of CO, in the presence of Pd(PPh 3 ) 4 as catalyst and AcOCs as base (Scheme 33). Mechanistically, the process is similar to that seen in Scheme 29, with CO in place of the isocyanide (and without the final rearrangement step) (Scheme 33).
Palladium-catalyzed incorporation of CO and CO2 into 2-iodoanilines to give isatoic anhydrides 31 has also been reported [110]. Reactions were carried out in THF at 60 °C under 1 MPa of CO2 and 0.5 MPa of CO, in the presence of Pd(PPh3)4 as catalyst and AcOCs as base (Scheme 33). Mechanistically, the process is similar to that seen in Scheme 29, with CO in place of the isocyanide (and without the final rearrangement step) (Scheme 33). Scheme 33. Synthesis isatoic anhydrides 31 from 2-iodoanilines.
In 2009, Correa and Martín reported the first example of palladium-catalyzed carboxylation of aryl bromides to benzoic acids 32 [111]. Reactions were carried out with Pd(OAc)2 as the catalyst precursor in the presence of tBuXPhos as ligand (tBuXPhos = ditert-butyl (2',4',6'-triisopropyl-[1,1'-biphenyl]-2-yl)phosphine) and 2 equiv of Et2Zn as reductant, in DMA/hexanes at 40 °C and under 10 atm of CO2 (Scheme 34). The proposed mechanism involves the oxidative addition of the aryl bromide to the in situ formed Pd(0), followed by carbon dioxide insertion and transmetallation with Et2Zn to give a zinc carboxylate I and an Et-Pd-Br species. Reductive elimination from the latter then regenerates Pd(0), while the benzoic acid product is obtained from zinc carboxylate following acidic work-up (Scheme 34). In 2009, Correa and Martín reported the first example of palladium-catalyzed carboxylation of aryl bromides to benzoic acids 32 [111]. Reactions were carried out with Pd(OAc) 2 as the catalyst precursor in the presence of tBuXPhos as ligand (tBuXPhos = di-tert-butyl(2 ,4 ,6 -triisopropyl-[1,1 -biphenyl]-2-yl)phosphine) and 2 equiv of Et 2 Zn as reductant, in DMA/hexanes at 40 • C and under 10 atm of CO 2 (Scheme 34). The proposed mechanism involves the oxidative addition of the aryl bromide to the in situ formed Pd(0), followed by carbon dioxide insertion and transmetallation with Et 2 Zn to give a zinc carboxylate I and an Et-Pd-Br species. Reductive elimination from the latter then regenerates Pd(0), while the benzoic acid product is obtained from zinc carboxylate following acidic work-up (Scheme 34). More recently, the first visible-light driven carboxylation of aryl halides (chlorides or bromides) to give methyl benzoates 33, catalyzed by Pd(0) in conjunction with Ir(ppy)2(dtbpy)(PF6) as a photoredox catalyst (dtbpy = 4,4'-di-tert-butyl-2,2'-bipyridine), has been reported [112]. The optimized conditions involved the use of Pd(OAc)2 as the Pd(0) precursor, t-BuXPhos (with aryl chlorides) or PhXPhos (with aryl bromides; PhXPhos = 2-diphenylphosphino-2′,4′,6′-triisopropylbiphenyl) as ligand, in the presence of Cs2CO3 as base and DIPEA (DIPEA = N,N-diisopropylethylamine) as electron-donor species, in DMA as the solvent at r.t. and under 1 atm of CO2. The initially formed carboxylates were converted into the methyl esters by acidic quenching and subsequent reaction with TMSCHN2 (Scheme 35). This method avoids the use of metallic reductants (such as Et2Zn, seen before, Scheme 34) and is also compatible with aryl chlorides, unreactive under the conditions of Scheme 34. It is worth noting that the carboxylation of aryl halides with carbon dioxide can also be catalyzed by first-row transition metals, including copper [113], nickel [114], and cobalt [115] catalysts. However, only palladium catalysis seems to be compatible with visible light-promoted conditions so far. A possible mechanism starts with the oxidative addition of the aryl halide to Pd(0), followed by reversible CO2 inser-Scheme 34. Synthesis of benzoic acids 32 from aryl bromides.
More recently, the first visible-light driven carboxylation of aryl halides (chlorides or bromides) to give methyl benzoates 33, catalyzed by Pd(0) in conjunction with Ir(ppy) 2 (dtbpy) (PF 6 ) as a photoredox catalyst (dtbpy = 4,4 -di-tert-butyl-2,2 -bipyridine), has been reported [112]. The optimized conditions involved the use of Pd(OAc) 2 as the Pd(0) precursor, t-BuXPhos (with aryl chlorides) or PhXPhos (with aryl bromides; PhXPhos = 2-diphenylphosphino-2 ,4 ,6triisopropylbiphenyl) as ligand, in the presence of Cs 2 CO 3 as base and DIPEA (DIPEA = N,N-diisopropylethylamine) as electron-donor species, in DMA as the solvent at r.t. and under 1 atm of CO 2 . The initially formed carboxylates were converted into the methyl esters by acidic quenching and subsequent reaction with TMSCHN 2 (Scheme 35). This method avoids the use of metallic reductants (such as Et 2 Zn, seen before, Scheme 34) and is also compatible with aryl chlorides, unreactive under the conditions of Scheme 34. It is worth noting that the carboxylation of aryl halides with carbon dioxide can also be catalyzed by first-row transi-tion metals, including copper [113], nickel [114], and cobalt [115] catalysts. However, only palladium catalysis seems to be compatible with visible light-promoted conditions so far. A possible mechanism starts with the oxidative addition of the aryl halide to Pd(0), followed by reversible CO 2 insertion. A single-electron reduction by an Ir(II) complex then takes place, with formation of a Pd(I) carboxylate species I and an Ir(III) species. The Pd(I) carboxylate finally undergoes a second single-electron reduction to give the aryl carboxylate with regeneration of Pd(0). The Ir(III) species is reconverted into Ir(II) by photoexcitation followed by the reaction of the excited Ir(III)* species with DIPEA (Scheme 35). species, in DMA as the solvent at r.t. and under 1 atm of CO2. The initially formed carboxylates were converted into the methyl esters by acidic quenching and subsequent reaction with TMSCHN2 (Scheme 35). This method avoids the use of metallic reductants (such as Et2Zn, seen before, Scheme 34) and is also compatible with aryl chlorides, unreactive under the conditions of Scheme 34. It is worth noting that the carboxylation of aryl halides with carbon dioxide can also be catalyzed by first-row transition metals, including copper [113], nickel [114], and cobalt [115] catalysts. However, only palladium catalysis seems to be compatible with visible light-promoted conditions so far. A possible mechanism starts with the oxidative addition of the aryl halide to Pd(0), followed by reversible CO2 insertion. A single-electron reduction by an Ir(II) complex then takes place, with formation of a Pd(I) carboxylate species I and an Ir(III) species. The Pd(I) carboxylate finally undergoes a second single-electron reduction to give the aryl carboxylate with regeneration of Pd(0). The Ir(III) species is reconverted into Ir(II) by photoexcitation followed by the reaction of the excited Ir(III)* species with DIPEA (Scheme 35). In a similar way, recently aryl triflates have been converted into benzoic acids 32 by Pd(0)-catalyzed, visible light-promoted carboxylation, carried out in the presence of Pd(OAc)2 as the catalyst precursor, DavePhos as ligand [DavePhos = 2-dicyclohexylphosphino-2'-(N,N-dimethylamino)biphenyl] and Ir(ppy)2(dtbpy)PF6 as photoredox cocatalyst (ppy = polypyrrole) [116]. Reactions were carried out under conditions similar to Scheme 35. Synthesis of methyl benzoates 33 from aryl halides.
In a similar way, recently aryl triflates have been converted into benzoic acids 32 by Pd(0)-catalyzed, visible light-promoted carboxylation, carried out in the presence of Pd(OAc) 2 as the catalyst precursor, DavePhos as ligand [DavePhos = 2-dicyclohexylphosphino-2 -(N,Ndimethylamino)biphenyl] and Ir(ppy) 2 (dtbpy)PF 6 as photoredox cocatalyst (ppy = polypyrrole) [116]. Reactions were carried out under conditions similar to those seen above for aryl halides, namely, at r.t. and atmospheric pressure of CO 2 , in DMA as the solvent and in the presence of Cs 2 CO 3 as base and DIPEA as electron donor (Scheme 36).
x 19 of 23 those seen above for aryl halides, namely, at r.t. and atmospheric pressure of CO2, in DMA as the solvent and in the presence of Cs2CO3 as base and DIPEA as electron donor (Scheme 36).

Conclusions
The versatility of palladium-based catalysts has been successfully exploited also in the efficient conversion of carbon dioxide into high value added organic molecules of applicative and pharmacological interest. Many different important Pd-catalyzed carboxylation processes have been developed and discussed in this review, mainly based on Pd(0) catalysis, although important Pd(II)-catalyzed reactions have also been reported. Particularly important results have been achieved in the Pd(0)-promoted CO2 incorporation into small rings (such as suitably functionalized epoxides and aziridines) as well as into suitably functionalized alkenes, allenes, or alkynes, to give highly important heterocyclic derivatives, such as cyclic carbonates, oxazolidinones, etc. Under Pd(II) catalysis, particularly important results have been achieved with propargyl amines as substrates, with formation of oxazolidinones, which could also incorporate an exocyclic estereal function Scheme 36. Synthesis of benzoic acids 32 from aryl triflates.

Conclusions
The versatility of palladium-based catalysts has been successfully exploited also in the efficient conversion of carbon dioxide into high value added organic molecules of applicative and pharmacological interest. Many different important Pd-catalyzed carboxylation processes have been developed and discussed in this review, mainly based on Pd(0) catalysis, although important Pd(II)-catalyzed reactions have also been reported. Particularly important results have been achieved in the Pd(0)-promoted CO 2 incorporation into small rings (such as suitably functionalized epoxides and aziridines) as well as into suitably functionalized alkenes, allenes, or alkynes, to give highly important heterocyclic derivatives, such as cyclic carbonates, oxazolidinones, etc. Under Pd(II) catalysis, particularly important results have been achieved with propargyl amines as substrates, with formation of oxazolidinones, which could also incorporate an exocyclic estereal function working in the presence of CO together with CO 2 under appropriate conditions. On this grounds, it is expected that in the future palladium will play a major role in CO 2 utilization and incorporation into suitable substrates, possibly in the presence of other promoting species (either metal-based or organo-based) as cocatalyst(s), which will allow us to achieve more demanding processes for the direct and selective synthesis of complex molecular architectures.
Author Contributions: All authors contributed equally to this review. All authors have read and agreed to the published version of the manuscript.
Funding: Financial support by MIUR PRIN 2017YJMPZN project (Mussel-inspired functional biopolymers for underwater adhesion, surface/interface derivatization and nanostructure/composite selfassembly-MUSSEL) to B.G. is acknowledged.